Devices, systems, and methods for peripheral arteriovenous fistula creation

ABSTRACT

Devices, systems and methods are disclosed for the formation of an arteriovenous fistula in the limb of the patient. Embodiments include an apparatus for the creation, modification and maintenance of a fistula, including the modification of an existing dialysis fistula; and a method of supplying oxygenated blood to the venous circulation of a patient. A kit of anastomotic implants is described which supports a broad base of patient anatomies and fistula locations. The devices, systems and methods can be used to treat patients with one or more numerous ailments including chronic obstructive pulmonary disease, congestive heart failure, hypertension, hypotension, respiratory failure, pulmonary arterial hypertension, lung fibrosis and adult respiratory distress syndrome.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of PCT/US06/29081, filed Jul.26, 2007, which claimed the priority of U.S. provisional application No.60/702,777, filed on Jul. 26, 2005, the full disclosures of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates generally to medical devices and methods.More particularly, the present invention relates to devices and methodsfor creating or modifying a flow of oxygenated blood into the venoussystem of a patient.

Chronic obstructive pulmonary disease affects millions of patients inthe United States alone. The present standard of care is oxygen therapy,which requires a patient to remain near a stationary oxygen source orcarry a bulky oxygen source when away from home or a treatment facility.It is easy to appreciate that such oxygen therapy has manydisadvantages.

Lung reduction surgery has recently been proposed for treating patientswith chronic pulmonary disease. Such surgery, however, is not a panacea.It can be used on only a small percentage of the total patientpopulation, requires long recovery times, and does not always provide aclear patient benefit. Even when successful, patients often continue torequire supplemental oxygen therapy.

There is therefore a need for improved approaches, including bothdevices and methods, for treating patients suffering from chronicobstructive pulmonary disease. If would be desirable if such devices andmethods were also useful for treating patients with other conditions,such as congestive heart failure, hypertension, lung fibrosis, adultrespiratory distress syndrome, and the like. Such devices and methodsshould provide for effective therapy, preferably eliminating the needfor supplemental oxygen therapy in the treatment of chronic obstructivepulmonary disease. There is a need for simplified procedural methodsthat limit patient risks and reduce procedure times. Improved Proceduresmust be developed to apply to a broad base of patient populations thatmay benefit from the therapy. At least some of these objectives will bemet by the invention described hereinafter.

BRIEF SUMMARY OF THE INVENTION

According to a first aspect of the invention, a method of treating apatient with chronic obstructive pulmonary disease (COPD) is disclosed.The distal end of a catheter device is placed into a first vessel of apatient, such as a vein or artery. The distal end of the catheter deviceis advanced from the first vessel to a second vessel at a location inthe limb of the patient, and subsequently withdrawn. A chronic flow ofblood between the first vessel and the second vessel is created througha fistula between the two vessels. In a preferred embodiment, thecatheter is flexible along a majority of its length, and the distal endof the catheter is intra-luminally advanced down the first vessel, or anadditional vessel in luminal communication with the first vessel, priorto the catheter entering the second vessel, such as an advancement overa guidewire that has already been placed between the first vessel andthe second vessel. The fistula created may be dilated to improve flowconditions, and preferably an anastomotic implant is placed to enhancelong-term patency of the fistula over time. In another preferredembodiment, the original catheter devices places the anastomotic implantafter being advanced from the first vessel to the second vessel. Thetherapeutic benefit of the described method is realized

In an alternative embodiment, energy is applied to the fistula, theenergy selected from the group consisting of: electrical energy such asradiofrequency or microwave energy; cryogenic energy; heat; radiation;and combinations thereof. In another alternative embodiment, an agent isdelivered to the fistula, such as an agent selected from the groupconsisting of: anti-proliferatives; anti-biotics; antithrombogenics; andcombinations thereof. In another embodiment, a flow rate is measuredprior to or after the creation of the fistula. Based on the results ofthe measurement, the fistula creation procedure and/or a fistulamodification procedure is adjusted to optimize the therapeutic benefitof the procedure and/or reduce risks or adverse events of the procedure.

In another preferred embodiment, the method further comprisesdetermining the location of the fistula. Numerous diagnostic andinformation gathering techniques may be employed such as visualizationtechniques including: angiography; venography; extra-vascularultrasound; intravascular ultrasound; Doppler ultrasound; and MRI. Thefistula site is determined based on one or more of: artery diameter;vein diameter; ratio of artery to vein diameter; distance between theartery and vein lumens; geometric relationship between the artery andvein lumens; distance from an arterial side branch; distance from anvenous side branch; arterial flow; venous flow; oxygen content inartery; oxygen content in vein; wall thickness of artery; wall thicknessof vein; degree of calcification of artery; degree of calcification ofvein; geometric relationship between the artery and vein lumens at thefistula site; hemodynamic factors; other parameters; and combinationsthereof.

The method of the present invention provides a medical treatment basedon one or more changes to patient physiology including but not limitedto: a decrease is systemic vascular resistance; an increase of thepartial pressure of O₂ dissolved in the arterial blood plasma, anincrease of the hemoglobin O₂ saturation in arterial or venous blood, anincrease of the O₂ concentration in arterial or venous blood; andcombinations of these. Flow of arterial blood to the venous through thesystem should exceed 5 ml/min, and is preferably greater than 50 ml/min.

The method of the present invention preferably utilizes a peripheralartery selected from the group consisting of: axillary; brachial; ulnar;radial; profundal; femoral; iliac; popliteal and carotid. The method ofthe present invention preferably utilizes a peripheral vein selectedfrom the group consisting of: saphenous; femoral; iliac; popliteal;brachial; basilica; cephalic; medial forearm; medial cubital; axillary;and jugular. The resultant fistula may have a circular or an ovalcross-section, such as an oval cross-section that has a major axisgreater than the diameter of either the artery or vein of the fistula.The method of the present invention preferably utilizes an anastomoticimplant placed between the two vessels such as an implant which providesone or more of the following functions: scaffolding an opening betweenthe first vessel and the second vessel; reducing neointimalproliferation into the fistula flow path; preventing tissue fromprotruding into the fistula flow path; placing a portion of the firstvessel wall in tension with the tissue of the second vessel wall;reducing bleeding of the tissue neighboring the fistula; enhancinghealing of the tissue neighboring the fistula; and combinations thereof.In a preferred embodiment, the anastomotic implant includes an activeagent, and may also include a covering or partial covering.

According to a second aspect of the present invention, a method oftreating chronic obstructive pulmonary disease in a patient isdisclosed. The method comprises the creation of a fistula in the limb ofthe patient, the fistula located between a first anatomical structureand a second anatomical structure. The first anatomical structurecontains blood at a first oxygen content level and the second anatomicalstructure contains blood at a lower oxygen content level. The secondanatomical structure provides blood to a lung of the patient. In apreferred embodiment, the fistula is created in a surgical procedure. Inan alternative, also preferred embodiment, the fistula is created in apercutaneous, interventional procedure.

In a preferred embodiment, a second fistula is created between a thirdanatomical structure and a fourth anatomical structure. The thirdanatomical structure contains blood at a first oxygen content level andthe fourth anatomical structure contains blood at a lower oxygen contentlevel. The second fistula is preferably in a limb of the patient.

In yet another preferred embodiment, the method further comprises theplacement of a guidewire from the first anatomical structure to thesecond anatomical structure, such as from an artery to a vein or a veinto an artery. This guidewire can be used to create or modify the fistulautilizing standard interventional “over-the-wire” techniques. In apreferred embodiment, the fistula is dilated to improve flow. In anotherpreferred embodiment, an anastomotic implant is placed within thefistula, such as an implant that is dilated after placement. In yetanother preferred embodiment, a second anastomotic implant is placedwithin the fistula, such as within all or a portion of the firstanastomotic implant. In yet another preferred embodiment, energy or anactive agent is applied to the fistula to improve the therapeuticbenefit and/or enhance long-term effectiveness.

In yet another preferred embodiment, the method further comprises theperformance of flow measurement procedure, such as a measurement madeprior to or after the creation of the fistula. Based on the measurement,the fistula site may be chosen or altered, or an already created fistulamay be modified such as via a dilation procedure or the placement of ananastomotic implant. In yet another preferred embodiment, the methodfurther comprises the determination of the fistula location. Additionaldiagnostic procedures may be performed prior to or during the fistulacreation procedure, such as a vessel visualization procedure includingbut not limited to: angiography; venography; extra-vascular ultrasound;intravascular ultrasound; Doppler ultrasound; and MRI. The fistulalocation is determined based on an analysis of a parameter selected fromthe group consisting of: artery diameter; vein diameter; ratio of arteryto vein diameter; distance between the artery and vein lumens; geometricrelationship between the artery and vein lumens; distance from anarterial side branch; distance from an venous side branch; arterialflow; venous flow; oxygen content in artery; oxygen content in vein;wall thickness of artery; wall thickness of vein; degree ofcalcification of artery; degree of calcification of vein; geometricrelationship between the artery and vein lumens at the fistula site;hemodynamic factors and combinations thereof.

The method of the present invention provides a medical treatment basedon one or more changes to patient physiology including but not limitedto: a decrease is systemic vascular resistance; an increase of thepartial pressure of O₂ dissolved in the arterial blood plasma, anincrease of the hemoglobin O₂ saturation in arterial or venous blood, anincrease of the O₂ concentration in arterial or venous blood; andcombinations of these. Flow of arterial blood to the venous through thesystem should exceed 5 ml/min, and is preferably greater than 50 ml/min.

The method of the present invention preferably utilizes a peripheralartery selected from the group consisting of: axillary; brachial; ulnar;radial; profundal; femoral; iliac; popliteal and carotid. The method ofthe present invention preferably utilizes a peripheral vein selectedfrom the group consisting of: saphenous; femoral; iliac; popliteal;brachial; basilica; cephalic; medial forearm; medial cubital; axillary;and jugular. The resultant fistula may have a circular or an ovalcross-section, such as an oval cross-section that has a major axisgreater than the diameter of either the artery or vein of the fistula.The method of the present invention preferably utilizes an anastomoticimplant placed between the two vessels such as an implant which providesone or more of the following functions: scaffolding an opening betweenthe first vessel and the second vessel; reducing neointimalproliferation into the fistula flow path; preventing tissue fromprotruding into the fistula flow path; placing a portion of the firstvessel wall in tension with the tissue of the second vessel wall;reducing bleeding of the tissue neighboring the fistula; enhancinghealing of the tissue neighboring the fistula; and combinations thereof.In a preferred embodiment, the anastomotic implant includes an activeagent, and may also include a covering or partial covering.

According to a third aspect of the present invention, a method oftreating chronic obstructive pulmonary disease in a patient isdisclosed. The method comprises the modification of a pre-existingdialysis fistula. In a preferred embodiment, the flow rate of thedialysis fistula is modified, such as a flow reduction procedureincluding the placement of an intra-luminal or extra-luminal device thatnarrows a portion of the flow path to reduce flow. In a preferredembodiment, the dialysis fistula includes an artificial graft, and theartificial graft lumen is narrowed to reduce flow. In an alternativeembodiment, the existing fistula flow rate is increased such as via adilation procedure.

According to a fourth aspect of the present invention, a method ofselecting an anatomical location for a fistula to be created between anartery and a vein is disclosed. The fistula is created to treat chronicobstructive pulmonary disease. The selection method includes theperformance of a vessel visualization procedure and measuring one ormore of the following at a proposed fistula location: artery diameter;vein diameter; ratio of artery to vein diameter; distance between theartery and vein lumens; geometric relationship between the artery andvein lumens; distance from an arterial side branch; distance from anvenous side branch; arterial flow; venous flow; oxygen content inartery; oxygen content in vein; wall thickness of artery; wall thicknessof vein; degree of calcification of artery; degree of calcification ofvein; geometric relationship between the artery and vein lumens at thefistula site; hemodynamic factors and combinations thereof.

According to a fifth aspect of the present invention, a kit for creatinga fistula to treat chronic obstructive pulmonary disease is disclosed.The kit includes an anastomotic implant that is selected from the groupconsisting of a first anastomotic implant and a second anastomoticimplant. The first anastomotic implant is for placement in a fistulabetween an anatomical structure containing oxygenated blood and ananatomical structure supplying blood to a lung of the patient. The kitfurther includes a second anastomotic implant for placement in a fistulabetween an anatomical structure containing oxygenated blood and ananatomical structure supplying blood to a lung of the patient. The firstanastomotic implant and the second anastomotic implant have differentgeometries, and either the first anastomotic implant or the secondanastomotic implant is implanted based on an analysis of one or morepatient parameters. In a preferred embodiment, the implant is chosenbased on one or more of the following: artery diameter; vein diameter;distance between the artery and vein lumens; distance from an arterialside branch; distance from an arterial side branch; arterial flow;venous flow; oxygen content in artery; oxygen content in vein; wallthickness of artery; wall thickness of vein; degree of calcification ofartery; degree of calcification of vein; geometric relationship betweenthe artery and vein lumens at the fistula site; hemodynamic factors; andcombinations thereof.

Both the foregoing general description and the following detaileddescription are exemplary and are intended to provide furtherexplanation of the embodiments of the invention as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various embodiments of thepresent invention, and, together with the description, serve to explainthe principles of the invention.

In the drawings:

FIG. 1 illustrates a fistula, created in the forearm of the patient,consistent with the present invention;

FIG. 2 illustrates fistula creation apparatus and method consistent withthe present invention;

FIG. 3 illustrates fistula creation apparatus and method consistent withthe present invention;

FIG. 4 illustrates fistula creation apparatus and method consistent withthe present invention;

FIG. 5 illustrates fistula creation apparatus and method consistent withthe present invention;

FIG. 6 is a cross sectional view of an anastomotic clip deploymentdevice and method consistent with the present invention;

FIG. 7 is a cross sectional view of an anastomotic clip deploymentdevice shown at a fistula creation site prior to full deployment of ananastomotic clip;

FIG. 8 is a cross sectional view of an anastomotic clip deploymentdevice shown at a fistula creation site prior to full deployment of ananastomotic clip;

FIG. 9 is a cross sectional view of a fistula creation site with ananastomotic clip deployed;

FIG. 10 illustrates a fistula treatment device, located in a fistulacreated in the thigh of the patient, with a consistent with the presentinvention;

FIG. 11 a illustrates an anastomotic clip consistent with the presentinvention;

FIG. 11 b illustrates another anastomotic clip consistent with thepresent invention;

FIG. 11 c illustrates yet another anastomotic clip consistent with thepresent invention;

DETAILED DESCRIPTION OF THE INVENTION

Reference will now be made in detail to the present embodiments of theinvention, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same reference numbers will be usedthroughout the drawings to refer to the same or like parts.

FIG. 1 depicts a peripheral arteriovenous fistula, fistula 110, createdin a patient, such as a human or other animal, between artery 130 andvein 120. Fistula 110 is located in the patient's forearm and providesoxygenated blood from the higher-pressure arterial system to the venoussystem such that blood flows from the artery 130 to vein 120 through andfistula 110. The fistula may be created in one or more of a set ofnumerous locations in the body of the patient, preferably in a limb toavoid unnecessary trauma and risk to a major, central vessel such as theAorta and Vena Cava. Applicable arteries for fistula 110 include but arenot limited to: axillary; brachial; ulnar; radial; profundal; femoral;iliac; popliteal; and carotid, preferably at a location where the arteryis approximately 4 mm or less in diameter and at least 2 mm in diameter.Applicable veins for fistula 110 include but are not limited to:saphenous; femoral; iliac; popliteal; brachial; basilica; cephalic;medial forearm; medial cubital; axillary; and jugular, preferable at alocation where the vein is at least 4 mm in diameter or less and atleast 3 mm in diameter. Fistula 110 is preferably at a location whereinthe two vessel walls are within 20 mm of one another, preferably lessthan 10 mm apart.

The forearm located arteriovenous fistula 110 of FIG. 1 is maintained ina fluidly open state by way of a vessel anastomotic clip, shunt device150. In alternative, also preferred embodiments, a fistula is createdwithout an anastomotic clip, such as a fistula created with theplacement of surgical sutures in an end-to-side or side-to-sideanastomosis of vessels. Numerous devices and methods can be employed tocreate the fistula of the present invention, such as vessel-to-vesselflow-channel creating devices including radio-frequency ablation and/orcoagulation devices, and artificial blood flow conduits including PTFEgrafts. In another preferred embodiment, an existing dialysis fistula ismodified to provide a therapeutic benefit other than dialysis access,such as treatment of a heart condition including COPD. Flow in theexisting dialysis fistula may be decreased, such as with the placementof an intra-luminal narrowing implant or extra-luminal impinging device,when the fistula is no longer to be accessed for dialysis, to improvetherapeutic benefit for the heart condition. Dialysis fistulas utilizingthe radial artery typically reach of flow rate between 600-1200 ml/min,which may be above the desired flow rate for the method of the currentinvention. Flow reduction procedures, as are described in detailhereinbelow, are appropriate for converting these fistulas from adialysis therapy fistula to a COPD therapy fistula.

Shunt device 150 is manufactured from one or more biocompatiblematerials and can provide numerous functions. Shunt device 150 canprovide tension between artery 130 and vein 120 at the fistula site tocreate a temporary or long-term fluid seal between the tissuesurrounding the openings in each vessel wall. Shunt device 150 canprovide sufficient radial force, either temporary or long-term, tomaintain a lumen between artery 130 and vein 120, such as a lumen with arelatively circular cross section or an oval cross section. An ovalcross section allows a larger cross sectional area such as that of anoval that has a major axis longer than the diameter of either the veinor artery at the fistula location. Shunt device 150 can act as a depotfor one or more pharmaceutical or other agents such as to enhancelong-term patency and biocompatibility. Also, shunt device 150 canprovide a control means to adjust the flow of blood from the arterialsystem to the venous system, either automatically or in combination witha separate device. Shunt device 150 can provide other functions such asto enhance the resultant therapeutic benefit of fistula 110 and/orprevent or reduce undesired side effects such as thrombus or atheromaformation, neointimal proliferation, vessel erosion and/or other adverseconditions.

Shunt device 150 has been placed in a surgical or interventionalprocedure, or a combination of the two. In an open surgical procedure, aclinician use scalpels and other cutting means to expose the associatedvessels to create fistula 110. Alternative, minimally invasive surgicalprocedures make use of one or more tubes, placed through small incisionsin the skin, through which the clinician can pass various visualizationand surgical tools to create the connection between the artery 130 andvein 120. In an interventional procedure, similar to balloon angioplastyand interventional atherectomy procedures, catheter devices are placedthrough introducer tools into one or more vessels, and advanced throughthe vasculature to a specific location by guided fluoroscopy, ultrasoundor other imaging equipment.

The flow of oxygenated blood from the arterial system through fistula110 to the venous system can provide therapeutic benefit to patientssuffering from one or more diseases including but not limited to:chronic obstructive pulmonary disease, congestive heart failure,hypertension, hypotension, respiratory failure, pulmonary arterialhypertension, lung fibrosis and adult respiratory distress syndrome. Thetherapeutic benefit results from one or more factors as is describedhereinbelow.

Blood returning to the right side of the heart is pumped to the lungswhere is becomes oxygenated or re-oxygenated before returning to theleft side of the heart to be pumped to the body's tissues via thearterial system. Blood flow experiences a resistance from all of thesystem vasculature, which is referred to as systemic vascular resistance(SVR). The re-circulated blood that passes through shunt device 150bypasses the peripheral microcirculation and decreases the SVR. Toachieve therapeutic benefit, a decrease of SVR of at least 5% would bedesired. Additional or alternative changes to patient physiology thatmay provide a therapeutic benefit include but are not limited to: anincrease of the partial pressure of O₂ dissolved in the arterial bloodplasma, an increase of the hemoglobin O₂ saturation in arterial orvenous blood, an increase of the O₂ concentration in arterial or venousblood; and combinations of these.

Blood flows through shunt device 150 from artery 130 to vein 120 becauseof the pressure gradient between the blood in the arterial system andthe blood in the venous system. In a preferred embodiment, the flowthrough shunt device 150 is at least 5 ml/min, and preferably greaterthan 50 ml/min. It may be desirable for shunt device 150 toself-regulate flow, or be controllable via internal or external means,as will be described in reference to subsequent figures hereinbelow. Theflow of arterial blood into vein 120 has cardiac, circulatory andrespiratory effects. Cardiac output increases with a decrease in SVR dueto the increased pressure gradient. This increase in cardiac outputcould benefit patients with cardiac failure or patients who suffer fromlow cardiac output, such as congestive heart failure patients.

Regarding respiratory effects, the oxygenated blood that mixes with thevenous blood already present in vein 120 results in a higher O₂concentration venous blood entering the right atrium of the heart andeventually the lungs. This high O₂ concentration venous blood leads toan increase in the O₂ concentration in arterial blood in two ways: (1)since the blood that is shunted does not have O₂ extracted by tissuecapillaries, the blood returning to the lungs has a higher O₂concentration after the creation of the shunt than before, and (2) thebinding of O₂ to the hemoglobin component of blood is more efficientwith a higher Pa O₂ (partial pressure of O₂ in arterial plasma)resulting in increased oxygen carrying capacity. These advantageousrespiratory effects could benefit patients with pulmonary arterialhypertension by lowering pulmonary arterial blood pressure, patientswith heart or respiratory failure by increasing arterial oxygenconcentration, or patients with chronic obstructive pulmonary disease byincreasing blood oxygen concentration.

Regarding circulatory effects, another important benefit of decreasingSVR is related to the fact that the lungs regulate their blood flowaccording to the O₂ content. An increase in the O₂ content shoulddecrease the pulmonary arterial blood pressure. These advantageouscirculatory effects could benefit patients with hypertension by loweringsystemic arterial, systolic and/or diastolic blood pressure. Thesecardiac, respiratory and circulatory effects could also benefit numerousother patients with circulatory or other diseases including but notlimited to: hypotension (by increasing cardiac output), lung fibrosis,adult respiratory distress syndrome, and the like.

Various interventional techniques can be used to create a fistula at ornear an artery and a vein a limb of the patient, such as in the forearmas is depicted in FIG. 1. In a preferred method, a fistula is createdbetween a starting vessel and a target vessel, wherein the startingvessel and target vessel consist of an artery and a vein or a vein andan artery, respectively. An arterial catheter is placed in the artery,and a venous catheter is placed in the Vein, at a location upstream ofthe fistula creation site. A crossing needle device that incorporates ahollow needle, advancable with controls at the device's proximal end, isplaced in the starting vessel, either an artery or a vein. Radiographicdye, or other contrast medium is injected through the catheter in thetarget vessel. The crossing needle of the crossing needle device isadvanced, the needle penetrating first the wall of the starting vesseland then the wall of the target vessel, eventually with the tip of theneedle residing within the lumen of the target vessel. A guidewire ispassed through the crossing needle down the lumen of the target vessel.An anastomotic clip delivery system, which may be the same as thecrossing needle device or a separate catheter, is advanced over thepreviously placed guidewire, and used to place an anastomotic clipbetween the starting vessel and the target vessel.

Referring to FIGS. 2 through 9, a method of creating a peripherallylocated fistula is described. Depicted in FIG. 2 is artery 130 and vein120, which travel to at least one location wherein their vessel wallsare in relative proximity to each other, such as within 20 mm of eachother. An introducer sheath, venous introducer 125 is placed through theskin of the patient, to provide access to Right Venous Iliac 122. Avenous catheter, imaging catheter 41, used for injecting contrast mediumand other agents, as well as the passage of guidewires and other devicesthrough an inner lumen, is placed through venous introducer 125 so thatits tip resides upstream to the intended location for the fistula,fistula site 111. This tip location allows radiographic dye or othercontrast medium injected through imaging catheter 41 to travel, with thevenous blood flow, past fistula site 111 and toward the heart of thepatient. Fistula site 111 is preferably chosen, at least in relativeproximity, prior to any incisions in the patient's skin. A non-invasivevessel visualization procedure, such as through the use of externalultrasound, allows numerous measurements to be performed including:visualization of vessel proximity and other geometric relationshipsbetween vessels and their lumens; vessel lumen diameter; vessel wallthickness and presence of calcification and other intra-luminalblockages; presence and relative location of vessel side-branches andbifurcations; and even blood flow rates through the use of Dopplerultrasound. Other applicable forms of vessel visualization, with orwithout prior an invasive procedure, includes: angiography; venography;X-ray; internal ultrasound including intravascular ultrasound; andmagnetic resonance imaging (MRI). Other diagnostic procedures, inaddition to the visualization procedures, may be performed to determinea location of the fistula of the present invention, including ameasurement of one or more blood parameters near the intended fistulalocation site 111, such as the amount of dissolved oxygen in the bloodpassing near the location.

A method of choosing the location for fistula site 111 is intended tomaximize therapeutic benefit, simplify the fistula creation procedure,improve long-term patency of the fistula, and/or reduce adverse eventsand undesired side effects. A preferred method includes an analysis ofone or more of: artery diameter; vein diameter; ratio of artery to veindiameter; distance between the artery and vein lumens; distance from anarterial side branch; distance from a venous side branch; arterial flow;venous flow; oxygen content in artery; oxygen content in vein; wallthickness of artery; wall thickness of vein; degree of calcification inartery; degree of calcification in vein; hemodynamic factors, and otherfactors.

A second introducer sheath, arterial introducer 135 is placed throughthe skin of the patient and into the artery. Catheter apparatus 10 isinserted through arterial introducer 135 and advanced to a locationproximate fistula creation site 111, such as at a starting location nearthe intended fistula creation site 111, or remote from site 111 such aspercutaneously entering a different artery and advanced to the intendedartery. Catheter apparatus 10 can provide numerous functions includingbut not limited to: injection of contrast medium including radiographicdyes and ultrasonic medium, injection of drugs or other agents,aspiration of blood, vessel to vessel needle advancement, visualizationof internal structures such as via ultrasound, fistula and/or implantdilation, fistula and/or implant contraction, tissue debulking,placement of an anastomotic clip, removal of an anastomotic clip,passage of guidewires and other small diameter devices, placement of afistula treatment device, placement of a anastomotic clip treatmentdevice, placement of a flow modification device, placement of avisualization device such as an intravascular ultrasound catheter andother functions. These various functions can be performed by or with theassistance of apparatus 10 through the use of functional elementsintegrated into apparatus 10, or separate devices which can be passedthrough one or more lumens accessible from the proximal end of apparatus10.

Located at the proximal end of apparatus 10 are various knobs that areused to rotate, advance, retract, manipulate, activate, or otherwisecontrol the slidable tubes, needles and other elements of apparatus 10.Sheath advancement knob 22 is mechanically connected to outer sheath 12that surrounds various internal tubes, elements and lumens. In apreferred embodiment, apparatus 10 includes a visualization element,such as an ultrasound element, not shown. The visualization element canproduce, through electronic or other means, a visual representation ofthe device and neighboring tissue. The visualization element may be anultrasound catheter, such as a rotational or fixed array ultrasoundcatheter, which creates a cross-sectional image of the area surroundingthe device. The ultrasound catheter can be inserted into a lumen ofapparatus 10, or may be an integrated ultrasound device that has as anarray of ultrasound crystals which are fixedly mounted along the distalportion of apparatus 10 and contain electronic connections that areconnected to a proximal handle of apparatus 10, these connections matingwith a standard ultrasonic viewing monitor. In an alternative oradditional, preferred embodiment, apparatus 10 includes one or morevisualization markers, such as radiographic markers or embedded agentssuch as barium sulfate, or ultrasonically visible markers, all notshown. These markers can be used to perform controlled advancements,retractions, rotations and other positioning of apparatus 10 during thefistula creation procedure.

An internal tube, core 11 is slidingly received within outer sheath 12and advancable and retractable through manipulation of core advancementknob 23. Core 11 has at its distal end, tip 21, which preferably has adilating tip shape, and is atraumatic. Tip 21 is advanced to fistulasite 111, by advancing apparatus 10 through arterial introducer 135.Within core 11 is another tubular device, a flexible, advancable needle,needle 30 that has attached at its proximal end, needle advancement knob24. Slidingly received within needle 30 is a standard interventionalguidewire, guidewire 42. Needle 30 may consist of an outer protectivesheath, not shown, with a flexible, advancable needle contained withinits lumen.

Tip 21 is positioned against the wall of artery 130 such that needle 30can be advanced from an artery, artery 130, to a vein, vein 120. In analternative, preferred embodiment, the procedure is performed from veinto artery, such as from vein 120 to artery 130. Prior to advancingneedle 30 out of tip 21, radiographic dye can be injected to visualizethe border of the starting vessel, artery 130, under fluoroscopy. Aninjection of contrast medium from a catheter in the target vessel canvisualize the border of the target vessel walls as well. Contrast mediumcan be injected through the lumen in needle 30, or via a separate lumenincorporated through the length of apparatus 10.

In the artery to vein approach depicted in FIGS. 2 through 5, the outersheath 12 can be positioned against the arterial wall, such as bydeflection means integral to apparatus 10, to provide support anddirectionality as needle 30 is advanced. Typical advancement distance ofneedle 30 is at least 2 mm, which can be controlled with markings orother control means located on the proximal end of apparatus 10, notshown. After the needle 30 is advanced, or partially advanced, acontrast medium injection can be performed through the lumen in needle30, to confirm access of the target vessel, vein 120.

Referring now to FIG. 3, needle 30 has been advanced from artery 130into vein 120 by advancing needle advancement knob 24. Advancement canbe rapid, such as via a needle injection mechanism incorporated into aproximal handle of apparatus 10, injection mechanism not shown, and theinjection can be performed in a single continuous advancement or inmultiple discrete steps. In the discrete step approach, access of thetarget vessel can be confirmed by repeat attempts at advancing orprobing of guidewire 42, and/or by injection of contrast medium throughthe lumen of needle 30 and/or by aspiration of blood through needle 30.Visual examination of blood color can indicate arterial or venous bloodwithdrawn to confirm access to artery or vein respectively. Whenproperly accessed, the distal portion of guidewire 42 can be advancedfrom artery 130 into vein 120, in either a superior or inferiordirection.

Referring now to FIG. 4, guidewire 42 has been advanced in a superiordirection into vein 120. Needle 30 is ready to be retracted, anddepending on the configuration of apparatus 10, either removed entirelyfrom a lumen of apparatus 10 or retracted to a less distal location butremaining within apparatus 10. In a preferred embodiment, an automaticretraction mechanism, such as a spring-loaded mechanism, not shown, isintegral to apparatus 10. In various preferred embodiments of thepresent invention, outer sheath 12 and its internal components areremoved, and a second catheter device of apparatus 10 is inserted overguidewire 42 to place an anastomotic clip. In alternative preferredembodiments of the present invention, outer sheath may be removed orpartially removed, to load an anastomotic clip delivery device. Inanother preferred embodiment, apparatus 10 and outer sheath 12 remain atthe location proximate fistula site 111, and an anastomotic clipdelivery device is available, either by being already in place, orloaded within a lumen of outer sheath 12. In a preferred embodiment, ananastomotic clip delivery device is inserted after needle 30 is removedfrom the lumen of outer sheath 12.

FIG. 5 depicts catheter 10 in a partially withdrawn position, theretraction being performed while maintaining and/or advancing guidewire24 such that a sufficient portion of guidewire 24 remains within vein120. In a preferred embodiment, catheter 10 is fully withdrawn, leavingguidewire 24 sufficiently advanced into vein 120, after which a separatecatheter is inserted over-the-wire to place an anastomotic clip. In analternative embodiment, catheter 10 includes the anastomotic clip and anexternally operable deployment mechanism. Prior to the placement of theanastomotic clip, the tissue between the lumens of the artery 130 andvein 120, such as the vessel wall tissues and tissue external to thewalls, may need to be expanded or dilated with one or more devices suchas a standard angioplasty balloon. Alternatively or additionally, it maybe desirous to remove a portion of this tissue utilizing one or moredebulking tools such as ablative tools or tissue cutting and removingtools. These various methods of enlarging the opening, or flow path,between the two vessels can be performed with catheter 10 or a separatecatheter; over needle 30 or over a needle assembly, not shown; overguidewire 42 after needle 30 or a needle assembly is retracted; orcombinations of these.

Apparatus 10 may include various flow path or channel creation means,described in more detail in reference to subsequent figures. Flow pathdilation elements may include the incorporation of a compliant ornon-compliant balloon, with an inflation lumen and port located on theproximal end of apparatus 10, all not shown. The balloon may beintegrated into a distal portion of the needle assembly, on a distalportion of outer sheath 12, on a distal portion of core 11, or on aseparate tubular device advancable through a lumen of apparatus 10, allnot shown. Debulking means may include one or more of an energy ablationdevice, such as a radiofrequency ablation element, either monopolar orbipolar, or a cutting element similar to a pull back cutting elementused in pull back atherectomy procedures. The debulking means can beadvanced from the starting vessel to the target vessel to perform thedebulking procedure, advanced to the target vessel first and then pulledback from the target vessel to the starting vessel to perform thedebulking procedure, or both. In all flow path creation and enlargementprocedures, the flow path creation and enlargement elements can beintegrated into one or more components of apparatus 10 or be included ina separate tubular structure advancable through a lumen of apparatus 10.These flow path creation and enlargement procedures are all performedover the guidewire placed from the starting vessel to the target vessel.

FIG. 6 depicts apparatus 200, an anastomotic clip deployment apparatusconsistent with the present invention. Apparatus 200 is a flexible,catheter device, which includes a sliding core, core 211, which has alumen, lumen 213, from its proximal end, not shown, to its distal end,to allow placement over a guidewire, such as guidewire 42 placed inFIGS. 2 through 5 in the forearm of the patient. In an alternativeembodiment, apparatus 200 may include a rigid portion along a majorityof its length. Apparatus 200 includes outer sheath 212, which surroundsand slidingly receives core 211. Located at or near the distal end ofapparatus 200, is a preloaded anastomotic clip, clip 250, which is aself-expanding device constrained by outer sheath 212 which can bedeployed to secure and create a fistula between an artery and a vein,such as an artery and vein in the forearm or the patient consistent withthe method continued from FIGS. 2 through 5, or at another location suchas the thigh of a patient or other peripheral vascular location. Clip250 can be deployed by advancing core 211 forward while maintainingouter sheath 212 in a relatively fixed position; by retracting sheath212 while maintaining core 211 in a relatively fixed position; or byboth advancing core 211 and retracting outer sheath 212. A deploymenttrigger and trigger mechanism, not shown, may be incorporated intoapparatus 200 such that the retraction and/or advancement steps areaccomplished by activating the trigger, such that timing, relativetiming, and advancement and retraction distances are predetermined bythe trigger mechanism. In a preferred embodiment, some amount ofadvancement and retraction are accomplished simultaneously.

FIG. 7 depicts apparatus 200 deployed over a guidewire, guidewire 242,which can be placed similar to guidewire 42 of FIGS. 2 through 5, suchthat it passes from a vein and artery in the forearm of a patient.Guidewire 242 is shown passing through arterial wall 231, and venouswall 221. Outer sheath 212 is shown passing through both arterial wall231 and venous wall 221 to assist in the deployment of clip 250. Inorder to cross through the vessel walls, apparatus 200 may include aflow path-enlarging element such as an integrated balloon element;and/or apparatus 200 may include a dilating slope on one or more distalends. Apparatus 200 of FIG. 7 depicts clip 250 being placed from arteryto vein, however it should be appreciated that a vein to arteryplacement can be similarly accomplished by apparatus 200 and wouldresult in a similarly placed clip 250.

In FIG. 7, catheter 200 is inserted over a guidewire, guidewire 242,such as a guidewire placed from a first vessel to a second vessel asdescribed in reference to FIGS. 2 through 5. In an alternativeembodiment, catheter 200 can be inserted without guidewire 242, such asthrough the use of visualization or other percutaneous techniques. Shownin FIG. 7, clip 250 is partially deployed with distal end 251 of clip250 expanded and pulled against venous wall 221. Deployment is initiatedsuch as by advancing core 211 while maintaining outer sheath 212 in afixed position; by retracting sheath 212 while maintaining core 211 in afixed position; or by both advancing core 211 and retracting sheath 212,preferably in a simultaneous movement. Proximal end 252 of clip 250remains constrained by outer sheath 212. During the deployment process,apparatus 200 or any portion of apparatus 200 can be retracted whileinjecting contrast medium. Contrast medium can be injected throughapparatus 200, or through a venous catheter or separate arterialcatheter. Contact of the distal end 251 of clip 250 can be confirmed byvisualizing bulging of either or both the venous wall 221 and thearterial wall 231 during a contrast medium injection.

In FIG. 8, clip 250 has been further deployed, and outer sheath 212retracted to expose venous wall 221 and arterial wall 231. In analternative embodiment, outer sheath 212 does not pass through arterialwall 231 and/or venous wall 221 and clip 250 is pushed through bothwalls during deployment.

FIG. 9 depicts a fully deployed clip 250, providing an anastomoticconnection between arterial wall 231 and venous wall 221 such as toprovide a flow path, or fistula, between an artery and vein such as anartery or vein in an arm or leg of the patient. Clip 250 can providenumerous functions as has been described hereinabove including but notlimited to: scaffolding an opening between the first vessel and thesecond vessel; reducing neointimal proliferation into the fistula flowpath; preventing tissue from protruding into the fistula flow path;placing a portion of the first vessel wall in tension with the tissue ofthe second vessel wall; reducing bleeding of the tissue neighboring thefistula; enhancing healing of the tissue neighboring the fistula; andcombinations thereof. In FIG. 9, guidewire 242 has been removed and theprocedure can be considered complete. In a preferred embodiment,guidewire 242 remains in place, and subsequent operations can beperformed to enhance the outcomes and/or therapeutic benefits of theprocedure, or to complete one or more other interventional proceduressuch as those performed in either the starting vessel, or target vesselby way of the starting vessel. A flow measurement procedure, as has beendescribed hereabove, may be performed, and flow adjusted such as throughfurther dilation of clip 250. The cross-section of the flow thru lumenof clip 250 may be circular or oval and shape, and the dilatingapparatus, such as a dilating balloon, have a similar cross-section. Inan alternative, preferred embodiment, clip 250 has additionalfunctionality to improve the long-term patency of the fistula orotherwise provide improved therapy to the patient. Improvedfunctionality of clip 250 may include the integration of an agent, suchas an antibacterial, anti-thrombogenic, anti-prolific, or other agent.Clip 250 may also a covering along a part or the entirety of its length,such as a covering consisting of one or more of:polytetrafluoroethylene; Dacron™ material; Nitinol™ alloy; stainlesssteel; urethane; polyethylene; silicone; carbon and carbon compounds.

During retraction of apparatus 200 or one of its components, a balloonintegrated on the core 211 of apparatus 200, not shown, may be inflatedto help bias clip 250 in an open position during retraction. Prior tocomplete retraction, a contrast medium injection from the arterial sidecan be used to assess blood flow through the fistula. In a preferredembodiment, guidewire 240 is not removed until proper flow and/orsufficient therapeutic benefit are confirmed. If flow is determined tobe insufficient, or even too great, subsequent procedures can beemployed to change the flow characteristics, such procedures describedin more detail hereinbelow.

FIG. 10 depicts a fistula modification procedure and apparatus such thatflow through the fistula can be increased or decreased, or othercharacteristics of the fistula can be improved or otherwise modified toprovide enhanced therapy to the patient. Shown in FIG. 10 is artery 130,such as the femoral artery, and vein 120 such as the femoral vein,located in the thigh of a patient, after a thigh-located fistula 310 hasbeen created using one or more techniques described in detail throughoutthis application. Anastomotic clip 350 has been placed between artery130 and vein 120 to provide and maintain long-term flow of highlyoxygenated arterial blood into the venous system. Placed in a rightfemoral vein is venous introducer 125, and an imaging catheter 41introduced through venous introducer 125 such that its tip resides at alocation upstream to fistula 310. Inserted into the left femoral arteryof the patient is arterial introducer 135, and fistula maintenanceapparatus 300. Fistula maintenance apparatus 300 is placed over aguidewire, guidewire 342, which passes through fistula 310, from arteryto vein, similar to the wires placed in the fistula creation proceduresdescribed hereinabove. In a preferred embodiment, guidewire 342 was theguidewire used to create fistula 310, and has remained in place sinceoriginally placed from artery 130 to vein 120. Alternatively, guidewire342 can be placed using standard interventional guidewire techniquesafter fistula 310 has been created. A pigtail catheter or other contrastmedium injection catheter, not shown, may be placed such that its tip issuperior to fistula 310, to visualize fistula flow with contrast mediuminjections.

Apparatus 300 includes outer sheath 312 that slidingly receives one ormore internal components within one or more internal lumens. Fistulatreatment device 360 is a catheter device including an inner lumensurrounding guidewire 342 such that as either fistula treatment device360 or apparatus 300 are advanced, the advancement tracks alongguidewire 342. Fistula treatment device 360 includes near its distalend, fistula treatment element 311 that has been advanced to remainwithin the inner diameter of clip 350 of fistula 310. Fistula treatmentelement 311 can take numerous forms to increase or decrease the flowthrough fistula 310, modify the structure of clip 350 or fistula 310,add or remove material or agents from fistula 310 or clip 350, orotherwise modify one or more characteristics or properties of clip 350or fistula 310.

In a preferred embodiment, fistula treatment element 311 is a balloonused to dilate clip 350 and fistula 310. Clip 350 may be constructed ofplastically deformable materials, either totally or partially, such thatdilation will expand those materials to a greater diameter. For example,clip 350 may include self-expanding material at its ends, andplastically deformable materials at its midsection that that dilationincreased the diameter of the midsection and resultant fluid pathway atone or more locations along the fistula. Dilation of a fullyself-expanding clip 350 may also be appropriate to allow furtherexpansion of clip 350 due to expansion and/or deformation of the tissuethat surrounds clip 350. Decrease in fistula flow can be accomplished bydecreasing the diameter at one or more locations along the fistula, suchas with a specialized device that pulls a portion of the midsection ofclip 350 towards a smaller diameter.

In another preferred embodiment, fistula treatment element 311 mayinclude deployment of a second implant, not shown, to increase ordecrease flow properties, to provide one or more drugs or agents, or tootherwise modify the fistula and/or clip 350. Placement of a secondimplant may be used to enhance scaffolding, prevent bleeding, reducelumen diameter and/or perform another function, and may also requiremultiple dilations to achieve the desired effect.

In another preferred embodiment, fistula treatment element 311 mayinclude an element to perform one or more of the following functions:covering a portion of the anastomotic clip, applying an agent such as ananti-biotic agent, anti-infective agent and/or anti-proliferative agent,applying a source of heat, applying a source of cooling, applying asource of energy such as electrical energy including radio-frequency ormicrowave energy; cryogenic energy; light; and radiation.

Modification of fistula 310 may be performed during the same procedurethat created fistula 310, such as within an hour of the creation offistula 310 and over the same guidewire used to deploy clip 350, or themodification procedure can be performed in a subsequent procedure suchas a procedure greater than twenty four hours from the creation offistula 310. In such a subsequent procedure, a new guidewire, introducedthrough either artery 120 or vein 130 can be manipulated, using standardinterventional techniques, to access the fistula and cross over to theconnected vessel, either in the same direction as used in fistulacreation or the opposite. Apparatus 300 can then be advanced over thevessel-to-vessel guidewire to perform the fistula modification ortreatment procedure.

Additional and/or alternative flow modification procedures can beperformed to increase or decrease flow of arterial blood into the venoussystem. For example, creation of a second fistula between the artery 130and vein 120, second fistula not shown, can be made to increase flow ofoxygenated blood to the venous system. The second fistula can be createdduring the same procedure as the first fistula creation procedure, suchas within an hour of the first fistula creation, or in a subsequentprocedure such as a procedure more than twenty-four hours from thecreation of the first fistula. The flow modification procedure can beperformed before the anastomotic clip is placed, or after it is inposition between the artery and vein. The second fistula canalternatively be created in a different location, such as in the limb ofthe patient or at a more central location.

Flow modifications procedures may be performed for multiple reasons,such as reasons derived from a measurement of one or more physiologicparameters including but not limited to: blood pressure, heart rate,cardiac output, pa O₂, O₂ saturation, mean systemic arterial pressure ormean systemic venous pressure, respiration, blood glucose, heart ratevariability or other heart or other physiologic parameter. The resultsof the analysis are compared to one or more clinical outcome targetvalues or other types of outcome target values, such that if one or moretargets are achieved, the procedure is complete and no flow modificationprocedures are performed at that time. If one or more target values arenot achieved, a flow modification procedure may be performed. While thismay be the last step of this assessment procedure, in a preferredembodiment, a repeat parameter measurement is performed, and flowmodifications repeated, until target values have been achieved. One ormore parameters can be measured and assessed in the method describedhereinabove. A first parameter may be used for initial assessment, and adifferent for a subsequent assessment. Physiologic measurements can beassessed individually, or in combination with one or more otherphysiologic parameters. Outcome target values can be based on a singlephysiologic measurement and analysis, or a combination of multipleanalyses to determine satisfactory flow conditions. The flowmodifications can be performed multiple times. Target levels can beadjusted based on patient condition, procedure time or other procedureparameter (e.g. amount of contrast medium used), or amount of flowmodifications performed. Other variables and parameters can be integralto or other otherwise impact the flow modification procedures includingbut not limited to: patient disease state, first outcome target level,second outcome target level, duration of procedure, number of flowmodification procedures performed, outcome of previous analysis ofphysiologic data, outcome of analysis of different set of physiologicdata, patient age or other patient parameter.

In a preferred embodiment, fistula maintenance apparatus 300 of FIG. 10includes a visualization element such as an external ultrasound element314. The visualization element may also be an ultrasound catheter, suchas a rotational or fixed array ultrasound catheter, which is inserted ina lumen of fistula maintenance apparatus 300, or may be an integratedultrasound device has as an array of ultrasound crystals which arefixedly mounted along the distal portion of fistula maintenanceapparatus 300 and contain electronic connections that are connected to aproximal handle of fistula maintenance apparatus 300 and mate with astandard ultrasonic viewing monitor, all not shown. In an alternative oradditional preferred embodiment, fistula maintenance apparatus 300 ofFIG. 10 includes one or more visualization markers, such as radiographicmarkers or embedded agents, or ultrasound markers, all not shown. Thesemarkers can be used to perform controlled advancements, retractions,rotations and other positioning of fistula maintenance apparatus 300during the fistula creation procedure.

In a preferred embodiment, fistula maintenance apparatus 300 is used tomodify an existing dialysis fistula. Apparatus 300 is used to improveflow conditions, such as to increase or decrease fistula flow after aflow measurement procedure has been performed and sub-optimal flowdetermined. To reduce flow, apparatus 300 may be used to place animplant to narrow a portion of the flow path, either intra-luminally orextra-luminally. If the dialysis fistula includes an artificial graft, aflow-impinging implant may be placed along side of the graft or aluminal narrowing device placed within the graft. To increase flow,apparatus 300 may dilate a portion of the flow path, and/or remove anarrowing device or some flow-narrowing tissue.

FIGS. 11 a, 11 b and 11 c depict different configurations of anastomoticclips consistent with the present invention, each providing differentproperties and configurations applicable to fistula site, patientanatomy and other patient parameter specifics. The fistulas of thepresent invention may be placed in one or more limbs or other locationswithin the patient and need to be designed and manufactured to support awide range of anatomical geometries and other physiologic factors tosupport a substantial patient population afflicted with COPD and otherapplicable disease states. Implants will be needed to support a range ofartery diameters, vein diameters, and distance between the lumens of theappropriate arteries and veins. Implants with a varied range of elasticforces, scaffolding surface areas, and flange geometries may be requireddepending on the tissue and tissue properties surrounding the fistula,including the muscular nature of vessel walls. Implants may also need tosupport varied ranges of: distance from an arterial side branch;distance from an arterial side branch; arterial flow; venous flow; wallthickness of artery; wall thickness of vein; degree of calcification ofartery; degree of calcification of vein; geometric relationship betweenthe artery and vein lumens at the fistula site; hemodynamic factors; andother factors.

Referring specifically to FIG. 11 a, anastomotic clip 250′ has a similarconfiguration to anastomotic clip 250 of FIGS. 6 through 9 is shown.Clip 250′, a continuous wire construction, has a flange 255′ at eachend, separated by length VSD1. Clip 250′ has luminal diameter D1. Clip250′ may be chosen for implantation in a therapeutic fistula of thepresent invention based on numerous properties including but not limitedto: length VSD1; diameter D1; elastic properties of the clip; plasticproperties of the clip; vessel tensioning forces; and other propertieschosen to correlate to the patient's anatomy and the fistularequirements. Length VSD1 correlates to the vessel separation distanceat the fistula site. Diameter D1 correlates to the intended luminaldiameter of the fistula.

Clip 255″, a dumbbell construction with a solid flow through lumen, hasa flange 255″ at each end, separated by length VSD2. Clip 250″ hasluminal diameter D2. Clip 250″ may be chosen for implantation in atherapeutic fistula of the present invention based on numerousproperties including but not limited to: length VSD1; diameter D1;covered nature of flow through lumen; rigidity of the clip; plasticproperties of the clip; vessel tensioning forces; and other propertieschosen to correlate to the patient's anatomy and the fistularequirements. Length VSD2 correlates to the vessel separation distanceat the fistula site. Diameter D2 correlates to the intended luminaldiameter of the fistula.

Clip 255′″, a wire framed construction with non-parallel flanged ends,has a flange 255′″ at each end, separated by length VSD3. Clip 250′″ hasluminal diameter D3 and relative angle between each flange 255″ is angleA. Clip 250′″ may be chosen for implantation in a therapeutic fistula ofthe present invention based on numerous properties including but notlimited to: angular alignment of the artery and vein at fistulalocation; length VSD3; diameter D3; rigidity of the clip; plasticproperties of the clip; vessel tensioning forces; and other propertieschosen to correlate to the patient's anatomy and the fistularequirements. Length VSD2 correlates to the vessel separation distanceat the fistula site. Diameter D2 correlates to the intended luminaldiameter of the fistula. Angle A correlates to the angular alignment ofthe artery and vein at the fistula location.

In a preferred embodiment, a kit is provided with multiple anastomoticclips such as clips 255′, 255″ and 255′″ of FIGS. 11 a, 11 b and 11 c.The clinician or other associated health care professional chooses whichparticular anastomotic clip to place in the therapeutic fistula of thepresent invention based on numerous physiologic parameters includingvascular geometry, vascular characteristics, and other patient ortherapy specific parameters such as those that can be measured ordiagnosed pre-procedurally or intra-procedurally.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the invention being indicated by the following claims.

1. A method of treating chronic obstructive pulmonary disease in apatient comprising: externally visualizing anatomical structures in alimb of the patient to determine a degree of calcification; selecting afirst anatomical structure and a second anatomical structure in the limbbased at least in part on the degree of calcification; creating afistula in the limb between a first anatomical structure and a secondanatomical structure at a location based at least in part on the degreeof calcification; wherein the first anatomical structure contains bloodat a first oxygen content level and the second anatomical structurecontains blood at a second oxygen content level, said first oxygencontent level greater than said second oxygen content level; and whereinthe second anatomical structure provides blood to a lung of the patient.2. The method of claim 1 wherein the fistula is created in a surgicalprocedure.
 3. The method of claim 1 wherein the fistula is created in aninterventional procedure.
 4. The method of claim 1 wherein theperformance of said method decreases systemic vascular resistance of thepatient.
 5. The method of claim 1, wherein said treatment is based on anincrease of the partial pressure of O2 dissolved in the arterial bloodplasma, an increase of the hemoglobin O2 saturation in arterial orvenous blood, or an increase of the O2 concentration in arterial orvenous blood.
 6. The method of claim 1 further comprising creating asecond fistula between a third anatomical structure and a fourthanatomical structure wherein the third anatomical structure containsblood at a first oxygen content level and the fourth anatomicalstructure contains blood at a second oxygen content level, said firstoxygen content level greater than said second oxygen content level. 7.The method of claim 6 wherein the second fistula is created in a limb ofthe patient.
 8. The method of claim 1 further comprising placing aguidewire between the first anatomical structure and the 2nd anatomicalstructure.
 9. The method of claim 1 further comprising dilating thefistula.
 10. The method of claim 1 further comprising inserting ananastomotic implant within the fistula.
 11. The method of claim 10further comprising placing a second anastomotic implant within thefistula.
 12. The method of claim 10 further comprising dilating thefistula after the anastomotic implant is placed.
 13. The method of claim1 further comprising the step of applying energy to the fistula.
 14. Themethod of claim 13 wherein the energy is selected from the groupconsisting of: electrical energy such as radiofrequency or microwaveenergy; cryogenic energy; heat; radiation; and combinations thereof. 15.The method of claim 1 further comprising delivering an agent to thetissue neighboring the fistula.
 16. The method of claim 15 wherein theagent is selected from the group consisting of: anti-proliferatives;anti-biotics; anti-thrombogenics; and combinations thereof.
 17. Themethod of claim 1 further comprising performing a blood flow measurementprocedure.
 18. The method of claim 17 wherein the blood flow measurementprocedure is performed prior to, after, or both prior to and after thecreation of the fistula.
 19. The method of claim 17 wherein a flowmeasurement procedure is performed after the creation of the fistula,and a flow modification procedure is performed.
 20. The method of claim19 wherein said flow modification procedure includes dilating thefistula.
 21. The method of claim 19 wherein said flow modificationprocedure includes placing an anastomotic implant within the fistula.22. The method of claim 1 wherein the fistula location is further basedon an artery with at least a 2 mm diameter.
 23. The method of claim 22wherein the fistula location is based on a vein with at least a 3 mmdiameter.
 24. The method of claim 1 wherein the fistula location isfurther based on a vessel separation of less than 20 mm.
 25. The methodof claim 1 wherein blood flows through the fistula at a flow rate of atleast 5 ml/min.
 26. The method of claim 1 wherein the first anatomicalstructure is an artery.
 27. The method of claim 26 wherein theanastomotic implant provides a function selected from the groupconsisting of: scaffolding an opening between the first vessel and thesecond vessel; reducing neointimal proliferation into the fistula flowpath; preventing tissue from protruding into the fistula flow path;placing a portion of the first vessel wall in tension with the tissue ofthe second vessel wall; reducing bleeding of the tissue neighboring thefistula; enhancing healing of the tissue neighboring the fistula; andcombinations thereof.
 28. The method of claim 26 wherein the artery isless than 4 mm in diameter.
 29. The method of claim 1 wherein the secondanatomical structure is a vein.
 30. The method of claim 29 wherein thevein is selected from the group consisting of: saphenous; femoral;iliac; popliteal; brachial; basilic; cephalic; medial forearm; medialcubital; axillary; and jugular.
 31. The method of claim 29 wherein thevein is less than 4 mm in diameter.
 32. The method of claim 1 whereinthe fistula has a circular cross section when said method is completed.33. The method of claim 1 wherein the fistula has an oval cross sectionwhen said method is completed.
 34. The method of claim 1 furthercomprising the step of placing an anastomotic implant between the firstanatomical structure and the second anatomical structure.
 35. The methodof claim 34 wherein the anastomotic implant provides a function selectedfrom the group consisting of: scaffolding an opening between the firstanatomical structure and the second anatomical structure; reducingneointimal proliferation into a fistula flow path; preventing tissuefrom protruding into a fistula flow path; placing a portion of a wall ofthe first anatomical structure in tension with the tissue of a wall ofthe second anatomical structure; reducing bleeding of the tissueneighboring the fistula; enhancing healing of the tissue neighboring thefistula; and combinations thereof.
 36. The method of claim 34 whereinthe anastomotic implant includes an agent selecting from the groupconsisting of: anti-bacterial; anti-thrombogenic; anti-prolific; andcombinations thereof.
 37. The method of claim 34 wherein the anastomoticimplant includes a covered portion along its length.
 38. The method ofclaim 37 wherein the covering is selected from the group consisting of:polytetrafluoroethylene; Dacron material; Nitinol alloy; stainlesssteel; and combinations thereof.